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ENDOCERVICAL/TRANSFORMATION ZONE CELLS IN PAP TESTING by Kenneth E. Youens, M.D. (Download PDF  pdf_button)


Before puberty, the junction between the squamous epithelium of the ectocervix and the columnar epithelium of the endocervix lies at or near the cervical os. Particularly during adolescence and pregnancy, changes in the size and shape of the uterus cause the squamocolumnar junction to shift outwards onto the vaginal part of the cervix. Exposure to the acidic environment of the vagina causes replacement of the delicate endocervical epithelium with hardier squamous epithelium, in a normal process called squamous metaplasia. It is within this area of metaplasia, called the transformation zone, that cervical intraepithelial neoplasia (CIN) and carcinoma most frequently develop.1 The presence of endocervical or squamous metaplastic cells in a Pap specimen indicates that this at-risk part of the cervix has been sampled.

The Bethesda System for Reporting Cervical Cytology is a set of guidelines for Pap test reporting used by most laboratories in the United States. Under the Bethesda System, an endocervical/transformation zone (EC/TZ) component is considered to be present if ten or more endocervical or squamous metaplastic cells are identi­fied in a Pap sample. Unless a woman has had a hysterectomy or a high-grade or malignant lesion is detected, the Bethesda System requires cytologists to indicate whether the EC/TZ component is present in the Pap test report.2

Under the current Bethesda System, Pap specimens lacking an EC/TZ component are not considered unsatisfactory for evaluation. Instead, the EC/TZ component (like partially obscuring blood or inflammation, air-drying artifact, or borderline cellularity) is considered a so-called "quality indicator," and is reported separately.2


Clinical Significance of an Absent EC/TZ Component
Data on the clinical significance of an absent EC/TZ component is conflicting. Several cross-sectional studies have suggested that abnormal squamous cells are more likely to be found in Pap specimens when an EC/TZ zone component is present. However, data from retrospective cohort and case-control studies do not support this conclusion. These studies show that women with specimens lacking EC/TZ are not more likely to develop squamous abnormalities on follow-up, and that women have no increase in false negative Pap test results when their specimens lack an EC/TZ component. Another potential concern is that Pap samples lacking an EC/TZ component may be less effective for detection of cervical adenocarcinoma, though clear evidence to support this conclusion is not yet available.3, 4

EC/TZ Absent: What Is The Next Step?
The American Society for Colposcopy and Cervical Pathology (ASCCP) has developed a set of recommendations for follow up of women with negative Pap tests lacking an EC/TZ component or which show other partially obscuring factors. According to the ASCCP guidelines, the preferred management for most women who lack an EC/TZ component on their negative Pap test and are undergoing routine screening is a repeat Pap test in 12 months.3 The guidelines suggest considering an early repeat test (generally at six months) for some women, particularly those who have had:

1. A previous squamous abnormality without two subse­quent negative Pap tests or a negative high-risk human

2. A positive HPV test within twelve months
3. A previous Pap with an unexplained glandular cell abnormality
4. Clinician inability to clearly visualize the cervix or sample the endocervical canal
5. Obscuring factors in consecutive Pap tests
6. Insufficient prior screening

Concurrent high-risk HPV test results may be available for women with negative Pap tests that lack an EC/TZ component. If the HPV test is negative, the guidelines suggest that the Pap test be repeated in twelve months (rather than extending the screening interval to three years in women older than 30 years). If the HPV test is positive, the guidelines recommend a repeat Pap test in six months.3

Women with abnormal Pap test findings (e.g. ASC-US, LSIL, AGC, ASC-H, HSIL) should be managed according to the usual guidelines for those cytologic results, regardless of whether EC/TZ cells are present.5


References

1. Robboy SJ, Bentley RC, Russell P, Anderson MC, Mutter GL, Prat J. Robboy’s Pathology of the Female Reproductive Tract. 2nd ed. Churchill Livingstone; 2008.
2. Solomon D, Davey D, Kurman R et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA. 2002;287:2114-2119.  

3. Davey DD, Cox JT, Austin RM et al. Cervical cytology specimen adequacy: patient management guidelines and optimizing specimen collection. J Low Genit Tract Dis. 2008;12:71-81.
4. Cibas ES, Ducatman BS. Cytology: Diagnostic Principles and Clinical Correlates. 3rd ed, Saunders; 2009.

5. Wright TC, Massad LS, Dunton CJ et al. 2006 consensus guidelines for the management of women with abnormal practices cytopathology and gynecologic Surgical Pathology. cervical screening tests. J Low Genit Tract Dis. 2007;11:201-222.